title: A mechanism for TCR sharing between T cell subsets and individuals revealed by pyrosequencing.
abstract: The human naive T cell repertoire is the repository of a vast array of TCRs. However, the factors that shape their hierarchical distribution and relationship with the memory repertoire remain poorly understood. In this study, we used polychromatic flow cytometry to isolate highly pure memory and naive CD8(+) T cells, stringently defined with multiple phenotypic markers, and used deep sequencing to characterize corresponding portions of their respective TCR repertoires from four individuals. The extent of interindividual TCR sharing and the overlap between the memory and naive compartments within individuals were determined by TCR clonotype frequencies, such that higher-frequency clonotypes were more commonly shared between compartments and individuals. TCR clonotype frequencies were, in turn, predicted by the efficiency of their production during V(D)J recombination. Thus, convergent recombination shapes the TCR repertoire of the memory and naive T cell pools, as well as their interrelationship within and between individuals.
authors.affiliation: Computational Biology Group, Centre for Vascular Research, University of New South Wales, Sydney, New South Wales 2052, Australia.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Venturi
authors.forename: Máire F
authors.initials: MF
authors.lastname: Quigley
authors.forename: Hui Yee
authors.initials: HY
authors.lastname: Greenaway
authors.forename: Pauline C
authors.initials: PC
authors.lastname: Ng
authors.forename: Zachary S
authors.initials: ZS
authors.lastname: Ende
authors.forename: Tina
authors.initials: T
authors.lastname: McIntosh
authors.forename: Tedi E
authors.initials: TE
authors.lastname: Asher
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Almeida
authors.forename: Samuel
authors.initials: S
authors.lastname: Levy
authors.forename: David A
authors.initials: DA
authors.lastname: Price
authors.forename: Miles P
authors.initials: MP
authors.lastname: Davenport
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Douek
mesh_terms: D000328:Adult; D002999:Clone Cells; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000276:immunology*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D007156:Immunologic Memory / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011995:Recombination, Genetic / Q000276:immunology; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D055815:Young Adult
chemical_list: D007135:Immunoglobulin Variable Region; D016693:Receptors, Antigen, T-Cell, alpha-beta